title: Potent inhibition of hepatitis B virus production in vitro by modified pyrimidine nucleosides.
abstract: 2',3'-Dideoxy-3'-fluorothymidine (FddThd), 2',3'-didehydro-2',3'- dideoxythymidine (ddeThd), and 3'-fluoro-5-methyl-deoxycytidine (FddMeCyt) are, in their triphosphate forms, selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase. We report that 0.3 microM FddThd, FddMeCyt, or ddeThd as well as 3'-chloro-5-methyl-deoxycytidine (ClddMeCyt) or 3'-amino-5-methyl-deoxycytidine (AddMeCyt) almost completely blocked production of hepatitis B virus (HBV) particles by HBV DNA-transfected cell line 2.2.15 in vitro. Only at an at least 10-fold-higher concentration was a cytotoxic effect observed. These results indicate that FddThd, FddMeCyt, ClddMeCyt, AddMeCyt, and ddeThd are potent anti-HBV agents in vitro.
authors.affiliation: Zentralinstitut für Molekularbiologie, Akademie der Wissenschaften der Deutschen Demokratischen Republik, Berlin-Buch, German Democratic Republic.
authors.forename: E
authors.initials: E
authors.lastname: Matthes
authors.forename: P
authors.initials: P
authors.lastname: Langen
authors.forename: M
authors.initials: M
authors.lastname: von Janta-Lipinski
authors.forename: H
authors.initials: H
authors.lastname: Will
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.forename: H
authors.initials: H
authors.lastname: Merz
authors.forename: B E
authors.initials: BE
authors.lastname: Weiler
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006824:Hybridization, Genetic / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D011741:Pyrimidine Nucleosides